This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Membrane proteins of eukaryotic cells are crucial for a broad range of processes including metabolism, cellular signaling, and the relay of neuronal signals. While approximately one quarter of human genes encode membrane proteins and ~60% of clinically approved pharmaceuticals target them, our understanding of the mechanisms of these proteins is limited by a scarcity of three-dimensional information. My laboratory is focused on understanding the mechanisms of eukaryotic ion channels - membrane proteins that regulate the flow of ions across cellular membranes. While considerable progress has been made in understanding the mechanisms of potassium ion channels from crystal structures, we lack a detailed understanding of channels selective for other ions such as sodium, calcium, or chloride. We aim to determine the crystal structures of such channels and combine this structural information with functional measurements in order to better understand the mechanisms of channel function. In the long run, we hope that this information will be useful for improving human heath.